Elian Fahed A, Are Ubah, Ghosh Sunita, Nuin Paulo, Footz Tim, McMullen Todd P W, Brindley David N, Walter Michael A
Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
Department of Medical Oncology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
Breast Cancer (Dove Med Press). 2021 Mar 1;13:171-188. doi: 10.2147/BCTT.S282860. eCollection 2021.
Forkhead box Q1 () has been shown to contribute to the development and progression of cancers, including ovarian and breast cancer (BC). However, research exploring expression, copy number variation (CNV), and prognostic value across different BC subtypes is limited. Our purpose was to evaluate mRNA expression, CNV, and prognostic value across BC subtypes.
We determined expression and CNV in BC patient tumors using RT-qPCR and qPCR, respectively. We also analyzed expression and CNV in BC cell lines in the CCLE database using K-means clustering. The prognostic value of expression in the TCGA-BRCA database was assessed using univariate and multivariate Cox's regression analysis as well as using the online tools OncoLnc, GEPIA, and UALCAN.
Our analyses reveal that mRNA is differentially expressed between different subtypes of BC and is significantly decreased in luminal BC and HER2 patients when compared to normal breast tissue samples. Furthermore, analysis of BC cell lines showed that mRNA expression was independent of CNV. Moreover, patients with low mRNA expression had significantly poorer overall survival compared to those with high mRNA expression. Finally, low expression had a critical impact on the prognostic values of BC patients and was an independent predictor of overall survival when it was adjusted for BC subtypes and to two other FOX genes, and .
Our study reveals for the first time that is differentially expressed across BC subtypes and that low expression of is indicative of poor prognosis in patients with BC.
叉头框Q1(FOXQ1)已被证明与包括卵巢癌和乳腺癌(BC)在内的癌症的发生和发展有关。然而,关于FOXQ1在不同BC亚型中的表达、拷贝数变异(CNV)及预后价值的研究有限。我们的目的是评估FOXQ1在BC各亚型中的mRNA表达、CNV及预后价值。
我们分别使用RT-qPCR和qPCR测定BC患者肿瘤中FOXQ1的表达和CNV。我们还使用K均值聚类分析了CCLE数据库中BC细胞系的FOXQ1表达和CNV。使用单因素和多因素Cox回归分析以及在线工具OncoLnc、GEPIA和UALCAN评估TCGA-BRCA数据库中FOXQ1表达的预后价值。
我们的分析表明,FOXQ1 mRNA在不同BC亚型之间存在差异表达,与正常乳腺组织样本相比,在管腔型BC和HER2患者中显著降低。此外,对BC细胞系的分析表明,FOXQ1 mRNA表达与CNV无关。此外,与高FOXQ1 mRNA表达的患者相比,低FOXQ1 mRNA表达的患者总生存期明显较差。最后,低FOXQ1表达对BC患者的预后价值有关键影响,在针对BC亚型和另外两个FOX基因FOXA1和FOXC1进行调整后,它是总生存期的独立预测因子。
我们的研究首次揭示FOXQ1在BC各亚型中存在差异表达,且FOXQ1低表达表明BC患者预后不良。